We propose to elucidate the mechanism of bile acid transport across the liver by studying the effects on biliary physiology of variations in bile acid structure. Bile acid transport will be studied directly by injecting radiolabeled pairs of bile acids into the portal vein of the anesthetized rat and collecting the label secreted via a bile fistula. This allows cmparison of rates of transport of different bile acids and ultimately a hierarchy of such rates can be established, and correlated with aspects of chemical structure. In the cat we will compare the effects of modified bile acid structure on biliary lipid secretion. Bile acids will be synthesized and infused IV and bile collected from a biliary fistula and analyzed for bile acid, phospholipid and cholesterol. Three bile acids will be compared in each animal. Again the relationship between physical structure of the bile acid and physiologic effect should give some insight into the mechanism of biliary lipid secretion. Part of the process of bile acid transport across the hepatocyte may involve protein binding. Our previous work has shown two fractions of hepatic cytosol protein which bind bile acid. We propose to characterize these fractions physicochemically and physiologically. The chemical characterization would involve column chromatography iso electric focussing and gel electrophoresis. Pure protein could be used for generating a radio immuno assay which will allow physiologic studies.